Mark Roschewski1, Kieron Dunleavy2, Jeremy S Abramson3, Bayard L Powell4, Brian K Link5, Prapti Patel6, Philip J Bierman7, Deepa Jagadeesh8, Ronald T Mitsuyasu9, David Peace10, Peter R Watson11, Wahid T Hanna12, Christopher Melani1, Andrea N Lucas1, Seth M Steinberg13, Stefania Pittaluga14, Elaine S Jaffe14, Jonathan W Friedberg15, Brad S Kahl16, Richard F Little17, Nancy L Bartlett16, Michelle A Fanale18, Ariela Noy19, Wyndham H Wilson1. 1. Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD. 2. George Washington University Cancer Center, Washington, DC. 3. Massachusetts General Hospital Cancer Center, Boston, MA. 4. Comprehensive Cancer Center of Wake Forest Baptist Health, Winston-Salem, NC. 5. University of Iowa Hospital and Clinics, Iowa City, IA. 6. University of Texas Southwestern, Dallas, TX. 7. University of Nebraska Medical Center, Omaha, NE. 8. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. 9. University of California Los Angeles Clinical AIDS Research and Education Center, Los Angeles, CA. 10. University of Illinois, Chicago, IL. 11. Kinston Medical Specialists, Kinston, NC. 12. University of Tennessee Medical Center, Knoxville, TN. 13. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD. 14. Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD. 15. Montefiore Medical Center, Bronx, NY. 16. Washington University School of Medicine, St. Louis, MO. 17. Division of Cancer Therapy and Diagnosis, National Cancer Institute, Bethesda, MD. 18. MD Anderson Cancer Center, Houston, TX, and Seattle Genetics, Seattle, WA. 19. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
Abstract
PURPOSE: Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS: We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS: Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION: Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
PURPOSE:Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS: We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS: Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION: Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
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